Hepatic Triglyceride Lipase Activity Research Articles

Molecular cloning of mouse hepatic triacylglycerol lipase: gene expression in combined lipase-deficient ( cld/cld) mice

cDNA clones coding for mouse hepatic triacylglycerol lipase (HL) were isolated from a mouse liver cDNA library with a human HL cDNA as a probe. The cloned HL cDNA of 1652 nucleotides predicts a mature protein of 488 amino acids preceded by a signal peptide of 22 amino acids. Two potential sites for N-glycosylation are identified, which are both conserved in rat and human HL. Combined lipase deficiency ( cld) is a recessive mutation in mice, which causes the functional deficiency of HL and lipoprotein lipase, the isolated cDNA was used to study the expression of HL gene in cld/cld mice. Northern blot analysis of total cellular RNA from livers of cld/cld and normal mice showed that there are two mRNA species for HL with the sizes of 1.8 and 1.9 kilobases in both groups. However, the mRNA for HL was more abundant in cld/cld than in normal mice. RNase A protection assay of HL mRNA suggested that the multiple mRNA species for HL in cld/cld and normal mice are generated by differential utilization of polyadenylation signals and that there is no mutation in the structural gene for HL in cld/cld mice. The present study supports our hypothesis that the defect of HL activity in cld/cld mice is caused by abnormal post translational modification or processing of the lipase.

Effect of simvastatin (MK-733) on plasma triacylglycerol levels in rats

The effect of simvastatin (MK-733), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma triacylycerol (TG) levels was studied in rats. Dietary administration of MK-733 (0.055%, w/w) for 7 days significantly (P < 0.05) reduced plasma TG levels by 30.6% associated with a 44.3% significant (P < 0.01) reduction in very low density lipoprotein TG (VLDL-TG) as compared to those in the concurrent control rats. Clofibrate (0.08%, w/w) also significantly (P < 0.05) decreased plasma TG levels by 26.1%. MK-733 did not affect the tricylglycerol secretion rate (TGSR) during 0–1.5 hr after administration of Triton WR-1339, but reduced it by 33.9% during 1.5–3.0 hr. Clofibrate also decreased TGSR during 1.5–3.0 hr. MK-733 increased lipoprotein lipase (LPL) activity in epididymal adipose tissue and thigh muscle by 36.3 and 55.0% respectively. MK-733 significantly (P < 0.05) increased LPL activity in the post-heparin plasma by 21.5%, although it did not affect hepatic triacylglycerol lipase (H-TGL) activity. Clofibrate did not affect LPL activity in the tissues or LPL and H-TGL activities in the post-heparin plasma. It is considered that the mechanism of plasma TG-lowering effect of MK-733 is the removal of VLDL-TG by an increase in LPL activity in the tissues as well as a decrease in the TGSR.

Ｐｏｓｔｈｅｐａｒｉｎ ｌｉｐｏｌｙｔｉｃ ａｃｔｉｖｉｔｙの昼夜変化と若年および中高年肥満のトリグリセライド代謝における役割

The diurnal changes in postheparin lipolytic activity (PHLA) were studied as on aspect of its physiological changes in eight healthy volunteers in a fasting state. Serum lipids and PHLA in obese males were measured to determine the etiology of obesity-associated hypertriglyceridemia with respect to triglyceride (TG) catabolism. In the healthy nonobese volunteers, the lipoprotein lipase (LPL) activity did not show any diurnal changes, but decreased with time during fasting. The hepatic triglyceride lipase (HTGL) activity underwent diurnal changes, and was high in the morning and low at night. Perceiving the metabolic difference between young obese individuals (obese since childhood) and middle-aged obese individuals (obese since adulthood), PHLA and serum lipids were simultaneously determined and examined from the aspect of TG catabolism in a young male group aged 17-27 and an older male group aged 35-62. The lower-age group consisted of 15 normal-weight men and 25 obese men with 11 years (mean) of a history of obesity. The higher-age group consisted of 15 normal-weight men and 25 obese men with 12 years of a history of obesity. No differences were found in total cholesterol and LDL-cholesterol between the normal-weight and obese individuals of both groups. However, HDL-cholesterol was significantly decreased, only in the obese individuals of the higher age group, compared to the normal-weight individuals of this group. Serum TG and insulin were significantly higher in the obese individuals than normal-weight individuals of both groups. In the obese individuals in both groups, a positive correlation was demonstrated between serum TG and insulin. This suggested the increased production of TG in association with hypertriglyceridemia. In addition, TG positively correlated with LPL and HTGL activities in young obese individuals, while a negative correlation was demonstrated only between TG and LPL activity in older obese individuals. These results indicated an age-related difference in TG catabolism in obese individuals with obesity-associated hypertriglyceridemia.

Hyperlipoproteinemia in Chronic Renal Failure: Pathophysiological and Therapeutic Aspects

Dyslipidemia of chronic renal failure is of multifactorial origin. Decreased activity of lipoprotein lipase and hepatic triglyceride lipase, peripheral insulin resistance, hyperparathyroidism and L-carnitine deficiency are the contributing factors. This results in a disturbed catabolism of chylomicron, accumulation of very-low-density (VLDL) and intermediate-density (IDL) lipoproteins as well as incompletely cleared remnant particles, whereas low-density lipoprotein (LDL) levels are diminished. There is current debate as to whether cardiovascular disease is accelerated and whether hyperlipidemia should specifically be treated. In addition, there have been few means of influencing these metabolic alterations. Drug incompatibility and consequently side effects render treatment difficult. The drugs that have been most tested for lipid lowering in chronic renal failure are the fibric acids. By their mode of action, they are the logical choice. Dose reduction overcomes major side effects such as myopathy and rhabdomyolysis. The second generation of fibric acid derivatives (gemfibrozil and beclobrate) show several advantages over formerly used derivatives. Treatment with lovastatin and simvastatin appears to be safe and is recommended in a minority of patients with predominantly elevations of LDL. HMG-CoA reductase inhibitors also lower remnant particles effectively in hemodialysis (HD) patients. L-Carnitine and low-molecular-weight heparin have been shown to influence VLDL rich in triglycerides in a subset of patients on HD. In posttransplant hyperlipidemia, diet remains the first course of action in all patients. When this approach fails, the new lipid-lowering agents, especially fibric acids, appear to be safe in short-term studies in azathioprine- and ciclosporin-treated patients. Lovastatin has been shown to be safe in stable renal transplant patients. Its toxicity seems to depend mainly on high ciclosporin whole blood through or plasma levels.

Differential regulation of hepatic triglyceride lipase and 3-hydroxy-3-methylglutaryl-CoA reductase gene expression in a human hepatoma cell line, HepG2.

The level of hepatic triglyceride lipase (H-TGL) synthesis and secretion was examined in response to changes in cholesterol biosynthesis in the human hepatoma cell line HepG2. Cells were first fed a lipoprotein-deficient serum-supplemented medium to eliminate exogenous cholesterol. Mevinolin, a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, was then added at a concentration (37 microM) which inhibited cholesterol biosynthesis by greater than 85% and decreased total cell cholesterol from 36.1 to 27.4 micrograms/ml of cell protein. Mevinolin treatment caused a 4.9 +/- 0.8-fold increase in the amount of H-TGL activity secreted into the medium, a 1.8 +/- 0.4-fold rise in H-TGL-specific mRNA, and a concurrent 14-fold increase in HMG-CoA reductase mRNA. Addition of 1 mM mevalonic acid to normal or mevinolin-treated cells raised the cellular cholesterol content and decreased the amount of secreted H-TGL activity to levels below control values. Mevalonic acid also prevented mevinolin-induction of H-TGL and HMG-CoA reductase mRNA, suggesting a common regulatory step for H-TGL and HMG-CoA reductase. Exposure of cells to mevinolin and 25-hydroxycholesterol together resulted in a marked repression of HMG-CoA reductase mRNA levels, whereas these conditions further enhanced the secretion of H-TGL activity and the expression of H-TGL mRNA. These results demonstrate a differential role for 25-hydroxycholesterol in the regulation of H-TGL and HMG-CoA reductase expression.

A sandwich-enzyme immunoassay for the quantification of lipoprotein lipase and hepatic triglyceride lipase in human postheparin plasma using monoclonal antibodies to the corresponding enzymes

We have developed a sandwich-enzyme immunoassay (EIA) for the quantification of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in human postheparin plasma (PHP) using monoclonal antibodies (MAbs) directed against the corresponding enzymes purified from human PHP. The sandwich-EIA for LPL was performed by using the combination of two distinct types of anti-LPL MAbs that recognize different epitopes on the LPL molecule. The immunoreactive mass of LPL was specifically measured using a beta-galactosidase-labeled anti-LPL MAb as an enzyme-linked MAb, an anti-LPL MAb linked with the bacterial cell wall as an insolubilized MAb, and purified human PHP-LPL as a standard. The sandwich-EIA for HTGL was carried out by using two distinct anti-HTGL MAbs that recognize different epitopes on HTGL. The limit of detection was 20 ng/ml for LPL and 60 ng/ml for HTGL. Each method yielded a coefficient of variation of less than 6% in intra- and inter-assays, and a high concentration of triglyceride did not interfere with the assays. The average recovery of purified human PHP-LPL and -HTGL added to human PHP samples was 98.8% and 97.5%, respectively. The immunoreactive masses of LPL and HTGL in PHP samples, obtained at a heparin dose of 30 IU/kg, from 34 normolipidemic and 20 hypertriglyceridemic subjects were quantified by the sandwich-EIA. To assess the reliability of the measured mass values, they were compared with the corresponding enzyme activities measured by selective immunoinactivation assay using rabbit anti-human PHP-LPL and -HTGL polyclonal antisera. Both assay methods yielded a highly significant correlation in either normolipidemic (r = 0.945 for LPL; r = 0.932 for HTGL) or hypertriglyceridemic subjects (r = 0.989 for LPL; r = 0.954 for HTGL). The normal mean (+/- SD) level of lipoprotein lipase mass and activity in postheparin plasma was 223 +/- 66 ng/ml and 10.1 +/- 2.9 mumol/h per ml, and that of hepatic triglyceride lipase mass and activity was 1456 +/- 469 ng/ml and 26.4 +/- 8.7 mumol/h per ml, respectively. The present sandwich-enzyme immunoassay methods make it possible to study the molecular nature of LPL and HTGL in PHP from patients with either primary or secondary hyperlipoproteinemia.

Lipoprotein lipase and hepatic triacylglycerol lipase activities in peripheral and skeletal muscle lymph.

We studied the interstitial fluid concentration of two lipid-metabolizing enzymes (lipoprotein lipase and hepatic triacylglycerol lipase) to determine their importance in interstitial modification of filtered lipoproteins. Despite the use of a very sensitive lipase assay (1 nmol of fatty acid release/ml/hr), lipase activities in plasma and in peripheral and skeletal muscle lymph from control dogs were below the sensitivity of our assay. After heparin injection, hepatic triacylglycerol lipase and lipoprotein lipase activities in plasma were similar. However, the postheparin hepatic triacylglycerol lipase activities in peripheral and skeletal muscle lymph were only 1.4% and 1.1%, respectively, those of plasma. This concentration is considerably less than the lymph concentration of albumin, which has a similar size to the lipases but has a lymph concentration of 30% to 40% of plasma. Lipoprotein lipase activity in peripheral lymph and skeletal muscle lymph was 2.7% and 4.8%, respectively, of plasma activity. Since lipoprotein lipase has a similar size as hepatic triacylglycerol lipase, the disproportionate amount of lipoprotein lipase in lymph as compared to hepatic triacylglycerol lipase could be due to heparin crossing the capillary endothelium and displacing lipoprotein lipase from peripheral cells. Injection of radioactive heparin confirmed that it does cross into the interstitial space in sufficient concentrations to displace lipase from peripheral cells. We conclude that most of the lipase found in lymph after heparin injection is derived from peripheral cells and not from plasma. Furthermore, hepatic triacylglycerol lipase does not play a role in high density lipoprotein remodeling in interstitial fluid. Therefore, it seems likely that the considerable remodeling of high density lipoprotein that we found previously results from its interaction with peripheral cells.

Development, food intake, and ethinylestradiol influence hepatic triglyceride lipase and LDL-receptor mRNA levels in rats.

The influence of development and ethinylestradiol on low density lipoprotein (LDL)-receptor mRNA and hepatic triglyceride lipase (HTGL) activity and mRNA levels was studied in rat liver and intestine. Intestinal LDL-receptor mRNA levels are maximal in the perinatal period, whereas liver LDL-receptor and HTGL mRNA levels are highest after weaning in adult life. All mRNA levels reach a maximum between day 15 and 20 when rats still consume a lipid-rich diet, and increase twofold during weaning. Liver and intestinal LDL-receptor mRNA levels are not influenced by ovariectomy, but increase after ethinylestradiol treatment. Liver LDL-receptor mRNA shows a dose-dependent increase after ethinylestradiol and a sevenfold rise in liver LDL-receptor mRNA is attained with a dose of 2000 micrograms/day. Intestinal LDL-receptor mRNA increases slightly more than twofold after ethinylestradiol and this increase is not dose-dependent. Changes in LDL-receptor mRNA are independent of changes in food intake induced by ethinylestradiol treatment, since they are still observed after pair-feeding. The ethinylestradiol-induced increases in LDL-receptor mRNA levels are reflected by decreased serum apoB levels. HTGL mRNA levels increase after ovariectomy and show a dose-dependent decrease after ethinylestradiol. Pair-feeding abolishes the increase seen after ovariectomy, while the estrogen-mediated decrease is attenuated. These alterations in HTGL mRNA are reflected by similar changes in liver HTGL activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone-Induced Changes in Lipid Metabolism

Hypothyroidism is a major cause of secondary hypercholesterolemia. Amiodarone treatment alters both the levels of serum lipids and thyroid hormones. We investigated whether the amiodarone-induced changes in lipid metabolism are related to the changes in thyroid hormone levels. Eighteen patients received amiodarone (31 +/- 3 g cumulative dose) for six weeks. Serum triglyceride, total-cholesterol, high density lipoprotein-cholesterol and its subfractions, apolipoproteins B and AI, and plasma post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. Amiodarone treatment caused significant increases in serum total-cholesterol (baseline 4.4 +/- 0.21 (SE), 6 weeks 5.12 +/- 0.26 mmol/l, P less than 0.01), in low density lipoprotein cholesterol (baseline 2.61 +/- 0.26, 6 weeks 3.36 +/- 0.21 mmol/l, P less than 0.05) and in apolipoprotein B (baseline 1.95 +/- 0.15, 6 weeks 2.26 +/- 0.13 mmol/l, P less than 0.01) concentrations. Serum high density lipoprotein and its subfractions, or apolipoprotein AI levels did not change. Plasma post-heparin lipoprotein lipase activity increased (baseline 137 +/- 21, 6 weeks 168 +/- 21 U/ml, P less than 0.01) while hepatic triglyceride lipase did not change. Amiodarone also caused an increase in serum thyroxine (baseline 110 +/- 8, 6 weeks 136 +/- 6 mmol/l, P less than 0.05), although values remained in euthyroid range. In summary, amiodarone therapy increased the concentrations of atherogenic lipoproteins in the serum similar to that seen in hypothyroidism. On the other hand the effect of amiodarone on lipoprotein lipase was opposite to that seen in hypothyroidism. Therefore, amiodarone-induced changes in lipid metabolism cannot be explained solely on the basis of the changes in circulating thyroid hormone levels.

Species, diet, and gender differences in plasma postheparin lipolytic activities in nonhuman primates. Relationships with plasma lipids and high density lipoproteins.

Studies were done in selected groups of nonhuman primates in which the diet (low fat and high fat as either polyunsaturated or saturated fat), gender, and species (African green monkeys and cynomolgus monkeys) were varied. Large differences in plasma lipid and lipoprotein concentrations were found among these groups, providing the opportunity to examine their relationships to postheparin lipolytic activities (PHLA) including lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). PHLA was measured in plasma drawn 20 minutes after injection of heparin (100 units/kg). The assay was done with a radioactive triglyceride emulsion, and LPL and HTGL activities were estimated after 1 M NaCl inhibition of the former. LPL activity was high in both species of monkeys, and HTGL activity was low; the ratio of HTGL/LPL was consistently less than 0.5. The mean values for LPL activity did not vary significantly among experimental groups, but significant negative correlations between LPL activity and plasma triglyceride concentration were found. Statistically significant diet, species, and gender differences in HTGL activities were found. In high-fat-fed compared to low-fat-fed animals, HTGL activities were higher, and high density lipoprotein (HDL) cholesterol concentrations and the percentages of HDL2b were also higher. African green monkeys had consistently higher HTGL activities than cynomolgus monkeys and had higher concentrations of HDL cholesterol and a greater proportion of HDL as the larger HDL2b subfraction. Significantly lower HTGL activities were found in females compared to males fed the low-fat diets, and females had a significantly greater proportion of total HDL in the HDL2b subfraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between Post-Heparin Plasma Lipases, Triglycerides and High Density Lipoproteins in Normal Subjects

The relationship between plasma lipids and lipoproteins and the lipolytic activities of post-heparin plasma lipoprotein lipase (LpL) and hepatic-triglyceride lipase (H-TGL) was examined in normal subjects. Seven males and six females were given a high fat diet [15% carbohydrate (CARB), 65% fat, 20% protein] for 2 weeks followed by 4 weeks of a high CARB diet (65% CARB, 15% fat, 20% protein). Changes in plasma triglyceride concentrations associated with diet were negatively correlated with changes in HDL-C (r = -0.533, P less than 0.001) and the HDL subfraction HDL2b (r = -0.308, P less than 0.001). The activity of LpL in post-heparin plasma was positively correlated with changes in plasma HDL-C (r = 0.668, P less than 0.001) and HDL2b (r = 0.457, P less than 0.001), and negatively with plasma triglycerides (r = -0.546, P less than 0.001). Changes in H-TGL activity were negatively correlated with changes in HDL2b (r = -231, P less than 0.05) and positively correlated with HDL-C (r = 0.326, P less than 0.01). These results in normal subjects provide further evidence that LpL and H-TGL are important enzymes in the metabolism of plasma lipoproteins and that changes in their activities contribute to plasma lipid and lipoprotein concentrations.

Atypical type III hyperlipoproteinemia in a patient with Ig A myelomatosis

We studied a 58-year-old woman with severe therapy-refractory hyperlipidemia, xanthomatosis, and multiple myeloma (immunoglobulin A, lambda light chain). The lipid disorder became evident about half a year prior to the expression of myelomatosis. Clinical symptoms were similar to those found in classical type III hyperlipoproteinemia but the underlying metabolic defect was different from the one described in this primary dyslipoproteinemia. The patient has the heterozygous apolipoprotein E3/2 phenotype and her VLDL-cholesterol/serum-triglyceride ratio is unusually low at 0.05. Evidence is given that the hyperlipoproteinemia is due to an impaired catabolism of intermediate density lipoproteins probably because of a reduced hepatic triglyceride lipase activity.

High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered

We examined the influence of aromatization of testosterone on serum high-density lipoprotein cholesterol (HDL-C) and postheparin plasma hepatic triglyceride lipase activity (HTLA) in men. Eighteen healthy lean nonsmokers (ages, 20 to 33) were administered androgens in a weekly total dose of 280 mg for 12 weeks in one of three groups: testosterone enanthate (TE) (280 mg/wk intramuscularly [IM]); TE (280 mg/wk IM) + testolactone (TL) (250 mg orally [PO] four times daily); or methyltestosterone (MeT) (20 mg PO twice daily). Serum testosterone achieved steady state levels by 4 weeks with >40 nmol/L (TE and TE + TL) and <15 nmol/L (MeT) while 17b-estradiol (E2) rose to >250 pmol/L (TE) or remained below 70 pmol/L (TE + TL and MeT). LH fell to less than 5 U/L (TE and TE + TL) but remained unchanged with MeT. By 4 weeks, HDL-C had decreased significantly from 1.20 ± 0.13 to 0.77 ± 0.13 mmol/L (MeT), from 1.18 ± 0.15 to 0.89 ± 0.13 mmol/L (TE + TL), and demonstrated no decrease in the TE group across the time course of the study. These changes were preceded by mean increases in HTLA of 102% (MeT) and 55% (TE + TL) over baseline, and no significant change with TE. The changes in HDL-C and HTLA returned to baseline within 2 weeks of steroid cessation. There were no changes in total cholesterol, triglycerides, or insulin in any group but, in the MeT group, apo AI levels decreased and low-density lipoprotein cholesterol (LDL-C) increased. After 12 weeks of treatment, sex hormone binding globulin (SHBG) levels were decreased to 37% (MeT), 54% (TE + TL), and 73% (TE) of baseline levels; these changes were evident by the second week of treatment and returned to baseline by the second week following treatment cessation. These results suggest that TE has little effect on HTLA but when a corresponding increase in E2 levels is prevented, HTLA increases. MeT, which is not metabolized to E2, produced the most dramatic HTLA increases, even at a dose that did not reduce serum LH; thus, hepatic specific properties of 17-alkylated androgens may further increase the atherogenic potential of this class of androgens.

高HDL血症の発症におけるコレステリルエステル転送蛋白および肝性リパーゼ活性の意義

高HDL血症の発症におけるコレステリルエステル転送蛋白および肝性リパーゼ活性の意義

Effects of Spirulina platensis on plasma lipoprotein lipase activity in fructose-induced hyperlipidemic rats.

The effects of Spirulina platensis on lipoprotein lipase activity and hepatic triglyceride lipase activity in post-heparin plasma were studied in fructose-induced hyperlipidemic rats. Male Wistar rats aged 3 weeks old (body weight, 54 g) were fed on the high-fructose diet (68%) or the high-fructose diets containing Spirulina at the level of 5, 10, and 15%, respectively, for 4 weeks. The dietary hyperlipidemia caused by the high-fructose diet was improved by Spirulina feeding, accompanied by a significant increase in the lipoprotein lipase activity in post-heparin plasma.

Effect of Alcohol on Lipoprotein Metabolism

The mechanism by which alcohol increases plasma total high density lipoproteins (HDLs) and HDL-cholesterol is unknown, but it may involve modulation of the lipolytic enzymes, hepatic triglyceride lipase (HTGL) and/or lipoprotein lipase (LPL) in hepatic and extrahepatic tissues. The modulation of HDL metabolism by alcohol may also be related to its potential to induce mixed function oxidases in liver microsomes. These possibilities were examined by a pair-feeding protocol in which rats were fed diets with 35% of the caloric content as ethanol; control groups received a diet with an isocaloric amount of sucrose or were fed chow ad libitum. Alcohol caused a significant decrease in HTGL activity of liver microsomes, but there was no significant effect of alcohol upon the activities of LPL in adipose tissue and heart muscle. The relative rates of mixed function oxidases, assayed in control liver microsomes using ethoxy-,pentoxy- and benzyloxy-resorufin as substrates, were benzyloxy greater than ethoxy greater than pentoxy. This order was not affected by alcohol, but the oxidation of ethoxy- and pentoxyresorufin was reduced in liver microsomes from the ethanol-fed group. HTGL synthesis and secretion were also measured using primary rat hepatocyte cultures isolated from animals on the above dietary regimes and maintained for up to 3 days in basal medium alone or supplemented with 10 mmol/l ethanol. In basal media the order of activity of extracellular HTGL, released by the addition of heparin, was sucrose-fed greater than chow-fed greater than ethanol-fed. The rate of HTGL secretion from hepatocytes was stimulated in ethanol-containing medium, and was greater in hepatocytes from the sucrose-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein, apolipoprotein, and lipolytic enzyme changes following estrogen administration in postmenopausal women.

To test whether estrogen can modulate the cholesterolemic response to an Occidental diet, six healthy postmenopausal women were studied for 84 days while ingesting a solid food diet of constant composition high in cholesterol content (995 mg/d). In the middle of the study, estrogen (17 alpha-ethinyl estradiol, 1 microgram/kg per day) was administered orally. Ingestion of the diet for the initial 28 days did not alter lipoprotein lipid or apolipoprotein (apo) levels. However, with just 4 days of estrogen use there were significant decreases in apoE (-36%), low density lipoprotein cholesterol (-26%), and postheparin plasma hepatic triglyceride lipase activity (HTGL) (-61%), and an increase in high density lipoprotein (HDL) triglyceride (72%). These changes persisted throughout the estrogen use. The percent change in HTGL with 4 days of estrogen correlated inversely with the percent change in HDL triglyceride (rs = -0.94). After 28 days of estrogen there were also significant increases in HDL cholesterol (21%), HDL2 cholesterol (42%), apoA-I (37%), and apoA-II (9%), and a decrease in apoB (-11%). The level of apoE at this juncture correlated inversely with the level of HDL cholesterol (rs = -0.90), and the levels of HTGL and apoA-I correlated with HDL2 cholesterol (rs = -0.89 and rs = 0.89, respectively). Thus, HTGL may play a role in both the early estrogen-related changes in HDL triglyceride and apoE and the late estrogen-related changes in HDL cholesterol, apoA-I, and apoA-II.

Lipid lowering effect of omega-3 fatty acids in genetically obese zucker rats

Omega-3 fatty acids (n-3 FA) are known to reduce blood lipid levels. Recent data, however, suggested that n-3 FA supplementation may worsen glycemic control in diabetic humans. This study was designed to explore the effects of n-3 FA feeding on lipid metabolism and glycemic control in a strain of genetically obese, hyperlipidemic rats. Lean and obese Zucker rats were fed a semi-purified diet made with either n-3 FA or corn oil (n-6, 10% w/w for both diets). After 16 weeks feeding, lean and obese rats fed the n-3 FA diet showed a significant reduction in blood triglyceride (TG) levels. Obese rats had significantly elevated TG levels in comparison with lean rats. Lean n-3 FA fed rats had elevated lipoprotein lipase activity in adipose tissue while hepatic triglyceride lipase activity was lowered by n-3 FA feeding in both lean and obese rats. Hepatic lipogenic enzyme activities were suppressed by fish oil feeding. However, fish oil feeding significantly increased hepatic gluconeogenic enzyme activity in lean rats. Therefore, n-3 FA feeding may exert different effects on blood lipid and glucose levels in lean and obese subjects.

Quantitative and qualitative changes of apolipoprotein AI-containing lipoproteins in patients on continuous ambulatory peritoneal dialysis

Using immunoaffinity chromatography, two species of apo-AI containing lipoproteins (AILp); lipoprotein containing apo-AI and apo-AII (Lp-AI/AII), and lipoprotein containing apo-AI, but no apo-AII (Lp-AI) were isolated from 13 female patients on continous ambulatory peritoneal dialysis (CAPD), then characterized. The results were compared with findings obtained in agematched normolipidemic (control I) and mild hypertriglyceridemic (control II) female subjects. In comparison with control I: In AILp, the levels of total cholesterol (TC), cholesteryl ester (CE) and phospholipid (PL), and the levels of apoE were significantly lower in the CAPD patients while the levels of triglyceride (TG) and apo-CIII were significantly higher in these patients. The levels of apo-AI and apo-AII did not differ between the CAPD and control subjects. In Lp-AI/AII, changes of TC, CE, PL, TG, and apolipoproteins were similar to those of AILp, except for the ratio of apo-AI/apo-AII and the level of apo-CII, which was higher in the CAPD patients. In Lp-AI, changes of TC, CE, PL, and TG were also similar to those of AILp and Lp-AI/AII, but the apo-AI level was significantly lower in the CAPD patients. In comparison with control II: In AILp, the levels of PL, apo-AI, apo-AII, and apo-E were significantly lower in CAPD patients, but the apo-CIII levels were significantly higher. In Lp-AI/AII, the levels of PL and apo-E were significantly lower in CAPD patients. Other apolipoprotein levels were significantly higher in the CAPD patients. In Lp-AI, the levels of PL, apo-AI, and apo-E were significantly lower, but the in apo-CIII level was significantly higher in CAPD patients. Activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in the CAPD patients were significantly lower than those in control I and control II. These findings suggest that differences in TC, CE, and TG between the CAPD patients and control I are a reflection of the higher triglyceride levels, whereas changes of PL and apolipoproteins are unique to CAPD patients. These qualitative and quantitative changes may be linked with lower activities of LPL and HTGL in the CAPD patients. The CAPD patients may well be at a high risk for atherosclerotic coronary heart diseases.

Role of hepatic-triglyceride lipase activity in the association between intra-abdominal fat and plasma HDL cholesterol in obese women.

Intra-abdominal fat content is an important variable in the association between regional body fat distribution and plasma high density lipoprotein (HDL) cholesterol levels. In the present study, we report on the role of plasma postheparin lipases as well as abdominal and femoral adipose tissue lipoprotein lipase activities in the association between body fat distribution and plasma lipoprotein levels. Postheparin plasma lipoprotein lipase (LPL), hepatic-triglyceride lipase (H-TGL), abdominal and femoral adipose tissue (AT)-LPL activities and plasma lipoprotein levels were measured after an overnight fast in a sample of 16 obese women (ages 36.0 +/- 6.1 years [mean +/- SD], percent body fat 46% +/- 6%). Computed axial tomography was used to assess body fat distribution. Plasma postheparin LPL activity was neither correlated with total adiposity nor with the level of intra-abdominal fat. Intra-abdominal fat deposition was, however, positively correlated with H-TGL activity (r = 0.66, p less than 0.005). Furthermore, covariance analysis showed that the association between intra-abdominal fat and H-TGL was independent from total adiposity. Plasma postheparin LPL and abdominal AT-LPL activities showed no significant correlation with plasma lipoprotein levels, whereas femoral AT-LPL activity was positively correlated with the HDL2 cholesterol/HDL3 cholesterol ratio (r = 0.51, p less than 0.05). H-TGL activity was, however, negatively correlated with HDL2 cholesterol (r = -0.60, p less than 0.05), but not with HDL3 cholesterol (r = -0.28, NS). These results suggest that the high H-TGL activity in obese women with excess deep abdominal fat could be responsible for the reduction in plasma HDL2 cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)